Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the third leading cause of cancer-related death worldwide. Contemporary advances in systemic and locoregional therapies have led to changes in peer-reviewed guidelines regarding systemic therapy as well as the possibility of downstaging disease that may enable some patients with advanced disease to ultimately undergo partial hepatectomy or transplantation with curative intent. This review focuses on all modalities of therapy for HCC, guided by modern-day practice-changing randomized data where available. The surgical management of HCC, including resection and transplantation, both of which have evolving criteria for what is considered biologically resectable and transplantable, as well as locoregional therapy (i.e., therapeutic embolization, ablation, radiation, and hepatic arterial infusion), are discussed. Historical and modern-day practice-changing trials evaluating immunotherapy with targeted therapies for advanced disease, as well as adjuvant systemic therapy, are also summarized. In addition, this article examines the critical dimension of toxicities and patient-oriented considerations to ensure a comprehensive and balanced discourse on treatment implications.

Significant advances have occurred in the locoregional and systemic therapy landscape for hepatocellular carcinoma (HCC), with the most notable being the introduction of immune checkpoint inhibitor (ICI) combinations. ICI combinations have significantly improved the overall survival of patients with unresectable HCC, affording median survival over 2 years and long-term survival exceeding 5 years in a subset of patients. Accordingly, there has been increased interest in the earlier application of systemic therapies, including (neo)adjuvant therapy in the perioperative setting or in combination with intra-arterial therapies. However, recent data failed to demonstrate improved recurrence-free survival with use of adjuvant ICI therapy. Conversely, 2 trials showed improved progression-free survival when ICI therapies were combined with transarterial chemoembolization, although data regarding the impact on overall survival are still immature. These improved outcomes raise several new questions, including which patients with liver-localized HCC should receive systemic therapy, how should this be sequenced or combined with other available therapies, and how to manage those patients with marked responses, including consideration of liver transplantation. These questions are often determined on a case-by-case basis and best made in a multidisciplinary manner considering several factors, including tumor burden, degree of liver dysfunction, performance status, and patient's long-term goals of care.

To report final results of a prospective study of stereotactic body radiation therapy (SBRT) in patients with previously untreated solitary primary hepatocellular carcinoma (HCC).

This prospective, single-arm, multicenter phase 2 trial recruited patients with HCC who were unsuitable for, or refused, surgery and radiofrequency ablation, with 3-year overall survival rates as the primary endpoint and survival outcomes and adverse events as secondary endpoints. The prescribed SBRT dose was 40 Gy in 5 fractions. The final data were analyzed in November 2022.

Between 2014 and 2018, 36 patients (median age, 73.5 years) were registered; enrollment was closed before full recruitment due to slow accrual. Overall, 34 patients were analyzed for efficacy evaluation after excluding 2 patients. The median tumor size was 2.3 cm. The median follow-up times for all patients and for survivors were 49 and 56 months, respectively. The 3-year overall survival rate was 82% (95% confidence interval, 65%-92%). The 3-year local control rate was 93% (95% confidence interval, 76%-98%). Grade 3 or higher SBRT-related nonlaboratory toxicities were observed in 4 patients (11%). No grade 5 adverse events were observed.

Final results of this phase 2 trial suggest the efficacy and safety of SBRT for newly diagnosed early-stage HCC that is unfit for other local therapies. Although this study was underpowered by the small number of registrations, the excellent results indicate that SBRT may be an alternative option for the management of early-stage HCC.

Transarterial radioembolization (TARE) is a recommended locoregional strategy for intermediate hepatocellular carcinoma (HCC), whereas, the effect is insufficient to reverse the immunosuppression tumor microenvironment, and the overall benefits for patients remain to be improved. In this study, a multifunctional microsphere (MS) 131I-ICT/R848-MS is developed to propose an approach combined with TARE, icaritin (ICT) and immune modulator resiquimod (R848). ICT and iodine-131 (131I) radiation can induce immunogenic cell death, which, in combination with R848, will boost dendritic cell (DC) maturation. Decellularized liver model and SPECT/CT imaging revealed high specificity and long retention of microspheres. Radioactive distribution of 131I in tumor on 7 d following 131I-MS injection was over 7 times of that in normal liver tissue (4.26 ± 1.21 % ID/g vs 0.57 ± 0.23 % ID/g). 131I-ICT/R848-MS embolization brought significant immune activation, where the ratio of cytotoxic T lymphocytes to regulatory T cells in tumor sites upregulated from 1.75 ± 0.20 to 24.31 ± 1.79, and DC maturation in lymph nodes increased from 8.90 ± 1.51 % to 34.70 ± 3.12 %. Enhanced anti-tumor efficacy with no relapse was proved in rat orthotopic N1S1 HCC models. These results demonstrated the great potential of this multifunctional embolic agent to treat HCC through transarterial radio-immuno-chemoembolization (TARICE).

Embolic and ablative locoregional therapies (LRTs) for hepatocellular carcinoma are widely used to cure, bridge, or downstage patients for more definitive therapies. Common ablative therapies include microwave ablation and radiofrequency ablation, while embolic options include transarterial chemoembolization and 90Y transarterial radioembolization. While these therapies can be highly effective for the appropriate stage of disease, LRTs can suffer from a high rate of posttreatment recurrences. Considerations for administration of specific therapies include disease burden and underlying liver function. Recent data on concomitant or adjuvant systemic therapy, with LRT, have the potential to improve disease control and improve outcomes in this high-risk patient population.

Current prognostic models for patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) are not extensively validated and widely accepted. We aimed to develop and validate a continuous model incorporating tumor burden and biology for individual survival prediction and risk stratification.

Overall, 4,377 treatment-naive candidates for whom TACE was recommended, from 39 centers in five countries, were enrolled and divided into training, internal validation, and two external validation datasets. The novel model was developed using a Cox multivariable regression analysis and compared with our original 6-and-12 model (the largest tumor size [ts, centimetres] + tumor number [tn]) and other available models in terms of predictive accuracy.

The proposed model, named the '6-and-12 model 2.0', was generated as 'ts + tn + 1.5×log10 alpha-fetoprotein (AFP)', showed good discrimination (C-index 0.674) and calibration (Hosmer-Lemeshow test p = 0.147), and outperformed current existing models. An easy-to-use stratification was proposed according to the different AFP levels (≤100, 100-400, 400-2,000, 2,000-10,000, 10,000-40,000, and >40,000 ng/ml) along with the corresponding tumor burden cutoffs (8/14, 7/13, 6/12, 5/11, 4/10, and any tumor burden); that is, if the AFP level was 400-2,000 ng/ml, the stratification should be low-(≤6)/intermediate-(6-12)/high-risk (>12) strata. Hence, it could divide the patients into three distinct risk categories with a median overall survival of 45.0 (95% CI, 40.1-49.9), 30.0 (95% CI, 26.1-33.9), and 15.4 (95% CI, 13.4-17.4) months (p <0.001) from low-risk to high-risk strata, respectively. These findings were confirmed in validation and subgroup analyses.

The 6-and-12 model 2.0 significantly improved individual outcome predictions and better stratified the candidates recommended for TACE; thus, this model could be used in both clinical practice and trial design.

In this international multicentre study, we developed and internally and externally validated a novel outcome prediction model for candidates with HCC who would be ideal for TACE. The model, called the 6-and-12 model 2.0, was based on 4,377 patients from 39 centers in five countries. The model offers individualized outcome prediction, outperforming the original 6-and-12 model score and other existing metrics across all datasets and subsets. Based on different levels of alpha-fetoprotein (AFP) and corresponding cut-offs of tumor burden, patients could be stratified into three risk strata with significantly different survival prognoses, which could provide a referential framework to control study heterogeneity and define the target population in future trial designs.

Primary liver cancers are tumors that develop from different liver cells. Hepatocellular carcinoma (HCC), which develops from hepatocytes, accounts for approximately 75-85% of primary liver cancers.HCC is the 6th leading cause of cancer worldwide and the 3rd leading cause of cancer-related death. Its incidence is low in northern Europe, but high in sub-Saharan Africa and the Far East, where both hepatotropic viruses and exposure to mycotoxins are. It complicates cirrhosis in over 90% of cases and is predominantly male.The prevalence of HCC is increasing due to improved diagnostic techniques and criteria, but also to the persistence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in adults. A worldwide increase in the incidence of steatopathy makes it the leading cause of liver disease worldwide, associated with alcohol abuse and/or steatohepatitis associated with metabolic dysfunction (MASH), including type 2 diabetes.Chronic hepatotropic viral infections, cirrhosis and chemical carcinogens combine to produce an annual incidence of 2-5% of hepatocellular carcinoma arising from cirrhosis. This justifies biannual surveillance of known cirrhosis, without which late diagnosis limits therapeutic options.Major advances have been made in curative treatment (liver transplantation, surgery, radiodestruction) and palliative treatment (chemo- or radioembolization, sorafenib chemotherapy or immunotherapy), depending on how early HCC is diagnosed (size, number of hepatic or extrahepatic lesions) and the severity of underlying liver disease and associated comorbidities.

The development of tumor is closely linked to inflammation. Therefore, targeting molecules involved in inflammation may be effective in predicting cancer prognosis. Transarterial chemoembolization (TACE) holds significant therapeutic significance in addressing hepatocellular carcinoma (HCC). At present, no studies have evaluated the predictive value of γ-glutamyl transferase to albumin ratio (GAR) on the prognosis of HCC undergoing TACE.

To explore the potential prognostic significance of the GAR in individuals undergoing TACE for HCC.

A total of 1231 patients from seven hospitals in China were randomized into a training cohort (n = 862) and a validation cohort (n = 369). To establish independent prognostic factors for overall survival (OS), we utilized multivariate and univariate Cox regression models. The best cut-off value of the GAR was determined with the X-tile software, with OS as the basis. Validations were performed using dual therapy cohort and triple therapy cohort.

X-tile software revealed a GAR threshold of 4.75 as optimal. Both pre- and post-propensity score matching analyses demonstrated that the median OS in the low-GAR group (< 4.75) was notably longer compared to the high-GAR group (≥ 4.75), showing results of 26.9 vs 9.8 months (P < 0.001) initially, and 18.1 vs 11.3 months (P < 0.001) after match. Furthermore, multivariate analysis identified GAR ≥ 4.75 as an independent prognostic factor (P < 0.001). The receiver operating characteristic curves for the nomogram showed area under receiver operating characteristic curves of 0.741, 0.747, and 0.708 for predicting 1-, 2-, and 3-year survival, respectively. Consistent findings were reiterated in the two cohorts involving TACE in combination with targeted therapy and TACE in combination with targeted therapy and immunotherapy. Calibration curve and decision curve analyses substantiated the model's relatively robust predictive capabilities.

Our study validates the effective prognostic capacity of the GAR-based nomogram for HCC patients undergoing TACE or TACE in combination with systemic therapy.

Hepatocellular carcinoma (HCC) is a common and deadly cancer, often diagnosed at advanced stages, limiting surgical options. Transcatheter arterial chemoembolization (TACE) is a primary treatment for inoperable and involves the use of drug-eluting microspheres to slowly release chemotherapy drugs. However, patient responses to TACE vary, with some experiencing tumor progression and recurrence. Traditional TACE uses agents like oil-based drug emulsions and polyvinyl alcohol particles, which can permanently block blood vessels and increase tumor hypoxia. Additionally, TACE can suppress the immune system by reducing immune cell numbers and function, contributing to poor treatment outcomes. New approaches, like TACE using degradable starch microspheres and hydrogel-based materials, offer the potential to create different tumor environments that could improve both safety and efficacy. In our research, we developed a composite hydrogel (IF@Gel) made of Poloxamer-407 gel and Fe3O4 nanoparticles, loaded with idarubicin, to use as an embolic material for TACE in a rat model of orthotopic HCC. We observed promising therapeutic effects and investigated the impact on the tumor immune microenvironment, focusing on the role of immunogenic cell death (ICD). The composite hydrogel demonstrated excellent potential as an embolic material for TACE, and IF@Gel-based TACE demonstrated significant efficacy in rat HCC. Furthermore, our findings highlight the potential synergistic effects of ICD with anti-PD-L1 therapy, providing new insights into HCC treatment strategies. This study aims to provide improved treatment options for HCC and to deepen our understanding of the mechanisms of TACE and tumor environment regulation.

Researches comparing laparoscopic liver resection (LLR) with microwave ablation (MWA) for 3-5 cm multifocal hepatocellular carcinoma (MFHCC) are rare.

From 2008 to 2019, 666 intrahepatic tumours in 289 patients from 12 tertiary medical centres in China were included in this retrospective study. Propensity score matching (PSM) was performed to balance variables between the two treatment groups over time frames 2008-2019 and 2013-2019 to observe the potential impact of advancements in intervention techniques on overall survival (OS), disease-free progression (DFS) of patients. complications, hospitalization, and cost were compared.

Among 289 patients, the median age was 59 years [interquartile range (IQR) 52-66]. 2008-2019, after PSM, the median OS was 97.4 months in the LLR group and 75.2 months (95% CI 47.8-102.6) in the MWA group during a follow-up period of 39.0 months. The 1-year, 3-year and 5-year OS rates in the two groups were 91.8%, 72.6%, 60.7% and 96.5%, 72.8%, 62.5% [hazard ratio (HR) 1.03, 95% CI 0.62-1.69, P =0.920]; The corresponding DFS rates were 75.9%, 57.2%, 46.9%, and 53.1%, 17.5%, 6.2% (HR 0.35, 95% CI 0.23-0.54, P <0.001). 2013-2019, the median OS time was not reached in either group during the 34.0 months of follow-up, the 1-year, 3-year and 5-year OS rates in the two groups were 90.2%, 67.6%, 56.7% and 96.5%, 76.7%, 69.7% (HR 1.54, 95% CI 0.79-3.01, P =0.210); The corresponding DFS rates were 69.6%, 53.9%, 43.3%, and 70.4%, 32.1%, 16.5% (HR 0.68, 95% CI 0.41-1.11, P =0.120). The incidence of major complications was similar in both groups (all P> 0.05). MWA had shorter intervention times, hospitalization, and lower costs.

For resectable MFHCC patients, LLR is preferable due to its lower recurrence rate. For patients who do not qualify for LLR, advances in ablation technology have promoted MWA as a promising alternative.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide with an average five-year survival rate in the US of 19.6%. With the advent of HBV and HCV treatment and prevention, along with the rising rates of obesity, nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome are set to overtake infectious causes as the most common cause of HCC. While surgical resection and transplantation can be curative when amenable, the disease is most commonly unresectable on presentation, and other treatment approaches are the mainstay of therapy. In these patients, locoregional therapies have evolved as a vital tool in both palliation for advanced disease and as a bridge to surgical resection and transplantation. In this review, we will be exploring the primary locoregional therapies for HCC in patients with NAFLD, including transarterial chemoembolization (TACE), bland transarterial embolization (TAE), transarterial radioembolization (TARE), and percutaneous ablation.

With continuous advancements in interventional radiology, considerable progress has been made in transarterial therapies for hepatocellular carcinoma (HCC) in recent years, and an increasing number of research papers on transarterial therapies for HCC have been published. In this editorial, we comment on the article by Ma et al published in the recent issue of the World Journal of Gastro intestinal Oncology: "Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable HCC". We focus specifically on the current research status and future directions of transarterial therapies. In the future, more studies are needed to determine the optimal transarterial local treatment for HCC. With the emergence of checkpoint immunotherapy modalities, it is expected that the results of trials of transarterial local therapy combined with systemic therapy will bring new hope to HCC patients.

Hepatocellular carcinoma (HCC) accounts for 90% of liver cancer cases worldwide and is currently the most quickly increasing cause of cancer-related deaths in the United States. The 5-year survival rate for primary liver cancer is estimated to be below 20%, and HCC mortality is expected to increase by 41% by 2040. Currently, surgical resection is the first-line approach to definitive treatment of early-stage HCC. However, the majority of patients present with late-stage, unresectable disease due to the asymptomatic nature of early HCC. For patients who present with unresectable HCC, locoregional therapies such as transarterial chemoembolization (TACE) represent an alternative approach to HCC treatment. TACE is a minimally invasive, catheter-based technique that allows for targeted delivery of chemotherapy to tumor sites while occluding tumor-feeding blood vessels. In appropriately selected patients, outcomes for TACE therapy have been shown to be more favorable than supportive care or conservative management. The increasing incidence and mortality of HCC, in addition to the late-stage presentation of most HCC patients, demonstrates the need to expand the role of locoregional therapies in the treatment of HCC. TACE represents an appealing approach to HCC management, including disease control, palliation, and potentially curative-intent strategies. In this review, we will describe the current utility of TACE in the treatment of HCC, characterize the outcomes of patients treated with TACE across different HCC stages, and outline future applications of TACE in the treatment paradigm.

CT-guided interstitial brachytherapy (iBT) radiotherapy has been established in the treatment of liver tumors. With iBT, hepatocellular carcinoma (HCC) lesions can be treated beyond the limits of thermal ablation (i.e., size and location). However, a comprehensive analysis of the efficacy of iBT in patients within and beyond thermal ablation limits is lacking.

A total of 146 patients with 216 HCC lesions have been analyzed retrospectively. Clinical and imaging follow-up data has been collected. Lesions were evaluated in terms of suitability for thermal ablation or not. The correlation between local tumor control (LTC), time to progression (TTP), overall survival (OS), and clinical and imaging parameters have been evaluated using univariable and multivariable Cox regression analyses.

LTC rates at 12 months, 24 months, and 36 months were 87%, 75%, and 73%, respectively. 65% of lesions (n = 141) were not suitable for radiofrequency ablation (RFA). The median TTP was 13 months, and the median OS was not reached (3-year OS rate: 70%). No significant difference in LTC, TTP, or OS regarding RFA suitability existed. However, in the overall multivariable analysis, lesion diameter >5 cm was significantly associated with lower LTC (HR: 3.65, CI [1.60-8.31], p = 0.002) and shorter TTP (HR: 2.08, CI [1.17-3.70], p = 0.013). Advanced BCLC stage, Child-Pugh Stage, and Hepatitis B were associated with shorter OS.

iBT offers excellent LTC rates and OS in local HCC treatment regardless of the limits of thermal ablation, suggesting further evidence of its alternative role to thermal ablation in patients with early-stage HCC.

The most common primary liver tumors are hepatocellular carcinoma and cholangiocarcinoma. They constitute the sixth most common neoplasia and the third cause of cancer-related deaths worldwide. Although both tumors may share etiologic factors, diagnosis, prognostic factors, and treatments, they differ substantially in determining distinctive clinical management. In recent years, significant advances have been made in the management of these neoplasms, particularly in advanced stages. In this review, we focus on the most relevant diagnostic, prognostic, and treatment aspects of both, hepatocellular carcinoma and cholangiocarcinoma, underlying their applicability in Latin America.

Liver cancer, the sixth most common cancer globally and the second-leading cause of cancer-related deaths, presents a critical public health threat. Diagnosis often occurs in advanced stages of the disease, aligning incidence with fatality rates. Given that established treatments, such as stereotactic body radiation therapy and transarterial radioembolization, face accessibility and affordability challenges, the emerging focus on cancer cell metabolism, particularly arginine (Arg) depletion, offers a promising research avenue. Arg-depleting enzymes show efficacy against Arg-auxotrophic cancers, including hepatocellular carcinoma (HCC). Thus, in this review, we explore the limitations of current therapies and highlight the potential of Arg depletion, emphasizing various Arg-hydrolyzing enzymes in clinical development.

Transarterial chemoembolization (TACE) is widely performed as a major treatment for hepatocellular carcinoma (HCC) patients, and there is a need to stratify patients for whom the most benefit from the treatment. This study aimed to develop a refined prediction model for overall survival (OS) in patients undergoing TACE as a first-line treatment in a large cohort and validate its performance.

A total of 2,632 patients with HCC of Barcelona Clinic Liver Cancer stage A or B who underwent TACE between 2008 and 2017 were enrolled. The patients were randomly assigned to a training cohort (n = 1,304) or a validation cohort (n = 1,328). Independent predictors of OS were used to develop a prediction model.

The median age of patients in the entire cohort was 63 years, with the majority having hepatitis B virus (56.6%) and being classified as Child-Pugh class A (82.4%). We developed a new prognostic model, called the TACE-prognostic (TP) score, based on tumor burden (sum of the largest tumor diameter and tumor number), alpha-fetoprotein, and Albumin-Bilirubin grade. Patients were classified into five risk groups according to TP scores, with median survival significantly differentiated in both training and validation cohorts (P < 0.001). The new model consistently outperformed other currently available models in both the training and validation cohorts.

This newly developed TP scoring system has the potential to be a useful tool in identifying ideal candidates of TACE and predicting OS with favorable performance and discrimination. However, further external validation is needed to confirm its effectiveness.

The application of immune checkpoint inhibitors (ICIs) has changed the treatment of advanced hepatocellular carcinoma. Transcatheter arterial chemoembolization (TACE) is a first-line treatment for intermediate hepatocellular carcinoma. Serving as a local treatment modality that can induce immunogenic cell death, the efficacy and safety of combined use with ICI have not been evaluated. Although there have been prospective studies aimed at evaluating the efficacy and safety of ICI combined with TACE in BCLC stage B HCC patients, there are few reports on the evaluation of BCLC stage C patients with distant metastasis or portal vein cancer thrombus. Data of unresectable hepatocellular carcinoma patients received PD-1 inhibitor and TACE were collected in Xijing Hospital from June 2019 to December 2022. The tumor response was evaluated according to the Solid Tumor Modified Response Evaluation Standard (mRECIST), including complete response (CR), partial response (PR), disease stability (SD), disease progression (PD), objective response rate (ORR), and disease control rate (DCR). The progression-free survival (PFS) and overall survival (OS) were used to estimate therapy efficacy. The treatment-related adverse events were evaluated based on National Cancer Institute Common Adverse Event Evaluation Criteria (CTCAE) version 5.0. A total of 42 patients with unresectable hepatocellular carcinoma were included in this study, including 34 males (80.5%) and 8 females (19.5%). The average age is 54.5 years, ranging from 34 to 72. The median follow-up time was 12.3 months, with an ORR of 42.9% and a DCR of 90.5% as of the follow-up time. The median PFS is 7.5 months (95% CI: 5.76-9.23), and the median OS has not yet been reached; 6-month PFS was 62.2%. Safety analysis showed that 41 (97.6%) patients experienced treatment-related adverse reactions, mainly including elevated AST and ALT, fever, elevated bilirubin, hypothyroidism, nausea, abdominal pain, and rash. 40 patients had grade 1/2 adverse reactions, and only one patient had grade 3 adverse reactions, manifested as intolerable rash, nausea, and vomiting. Treatment is terminated when symptomatic treatment and drug suspension cannot be alleviated. In this study, thre patients with unresectable hepatocellular carcinoma were treated with PD-1 inhibitor combined with TACE to achieve good tumor reduction effect and underwent liver cancer resection surgery. For patients with unresectable hepatocellular carcinoma, whether in BCLC stage B or stage C, effective systemic therapy (PD-1 inhibitor) combined with local therapy (TACE) can achieve a high rate of tumor regression and objective response. Some patients may even pursue surgical treatment opportunities, and the treatment-related adverse reactions are controllable, which is expected to provide new options for extending the survival of unresectable hepatocellular carcinoma patients.

The recurrence rate after curative resection for hepatocellular carcinoma (HCC) reaches over 70% after 5 years and early recurrence (within 1 year) is now recognized as having a poor prognosis and has limited treatment options.

We retrospectively reviewed 184 consecutive patients who underwent curative hepatic resection for HCC. Severe early recurrence was defined as multiple (beyond up-to-7) liver recurrence or distant metastasis after hepatic resection within 1 year. We divided the participants into two groups according to severe early recurrence and analyzed clinicopathological and long-term outcomes.

Among the patients with multiple or distant metastasis (n = 59), 49 patients (83%) had recurrence within 1 year. Overall survival (OS) and recurrence-free survival (RFS) were significantly worse in the severe early recurrence group than in the others group. Logistic regression analysis revealed that severe early recurrence was significantly associated with macroscopic vascular invasion (MVI), tumor burden score (TBS) > 4.70, and ALBI grade 2. In patients with scores of 2 and 3 (the sum of the three factors), OS and RFS rates were significantly poorer than those of patients with scores of 0 or 1. Positive predictive value and negative predictive value for severe early recurrence was 68.4% and 84.2%, respectively. Furthermore, a validation study demonstrated that cases with these factors were at high risk of severe early recurrence and had poor prognosis.

In this retrospective analysis, MVI, TBS, and ALBI could predict severe early recurrence after hepatic resection for HCC, and patients with these risk factors had a poor prognosis.

Local ablation therapy (LAT) is primarily recommended for solitary inoperable hepatocellular carcinomas (HCCs) of ≤3 cm in diameter. However, only two-thirds of uninodular small HCCs are suitable for LAT, and the second-best treatment option for managing these nodules is unclear. We aimed to compare the therapeutic outcomes of chemoembolization and radiotherapy in small HCCs unsuitable for LAT.

The study included 651 patients from a tertiary referral center who underwent planning sonography for LAT. These patients had 801 solitary HCCs of ≤3 cm in diameter and were treated with LAT, chemoembolization, or radiotherapy. Local tumor progression (LTP)-free survival and overall survival (OS) were measured according to the type of treatment of the index nodule.

LAT, chemoembolization, and radiotherapy were used to treat 561, 185, and 55 nodules in 467, 148, and 36 patients, respectively. LTP-free survival was significantly shorter in patients treated with chemoembolization than for those treated with LAT (multivariate hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.61 to 3.47) but not for those treated with radiotherapy (HR, 0.83; 95% CI, 0.38 to 1.83). However, OS was not affected by treatment modality. Matching and weighting analyses confirmed that radiotherapy gave comparable results to chemoembolization in terms of OS despite better LTP-free survival (HR, 2.91; 95% CI, 1.13 to 7.47 and HR, 3.07; 95% CI, 1.11 to 8.48, respectively).

Our data suggest that chemoembolization and radiotherapy are equally effective options for single small HCCs found to be unsuitable for LAT after sonographic planning. Betterfit indications for each procedure should be established by specifically designed studies.

Background: This is a retrospective study aimed at comparing the clinical efficacy and safety between drug-eluting bead transcatheter arterial chemoembolization (DEB-TACE) and conventional TACE (C-TACE) in the treatment of unresectable hepatocellular carcinoma. Methods: From July 2019 to April 2021, we enrolled 282 patients with unresectable hepatocellular carcinoma who were admitted to our hospital, of which 179 and 103 were in the DEB-TACE and C-TACE groups, respectively. General information was collected, and treatment effects were evaluated following the modified Response Evaluation Criteria in Solid Tumors. To compare the indexes of liver and kidney function, routine blood and coagulation were collected before treatment, and 1 day, 1 month, 3 months, and 6 months postoperatively. Postoperative adverse reactions (ie, fever, nausea, vomiting, anorexia, abdominal pain) were recorded to evaluate the safety of treatment. The two groups' progression-free survival and overall survival were also calculated to assess the treatment effect. Results: Preoperatively, the bilirubin, transaminase, and absolute neutrophil values between the two groups were not statistically significant (P > .05). At 1 month postoperatively, the absolute neutrophil values were significantly higher in the DEB-TACE group than those in the C-TACE group (P < .05). At 3 months postoperatively, AST, total bilirubin, and direct bilirubin levels were significantly elevated in the DEB-TACE group (P < .05), compared with the C-TACE group. However, at 6 months postoperatively, total and direct bilirubin levels in the C-TACE group were higher than those in the DEB-TACE group, showing a statistically significant difference (P < .05). For patients undergoing DEB-TACE, the survival risk was lower compared to those undergoing C-TACE. The survival risk of patients undergoing DEB-TACE was lower than that of C-TACE within 20 months postoperatively. The survival risk of patients undergoing DEB-TACE was lower than that of patients undergoing C-TACE. Conclusion: DEB-TACE may be superior to C-TACE in terms of safety and efficacy in the treatment of unresectable hepatocellular carcinoma.

The 10th Global Forum for Liver Magnetic Resonance Imaging was held in October 2021. The themes of the presentations and discussions at this Forum are described in detail in the review by Taouli et al (2023). The focus of this second manuscript developed from the Forum is on multidisciplinary tumor board perspectives in hepatocellular carcinoma (HCC) management: how to approach early-, mid-, and late-stage management from the perspectives of a liver surgeon, an interventional radiologist, and an oncologist. The manuscript also includes a panel discussion by multidisciplinary experts on three selected cases that explore challenging aspects of HCC management. CLINICAL RELEVANCE STATEMENT: This review highlights the importance of a multidisciplinary team approach in liver cancer patients and includes the perspectives of a liver surgeon, an interventional radiologist, and an oncologist, including illustrative case studies. KEY POINTS: • A liver surgeon, interventional radiologist, and oncologist presented their perspectives on the treatment of early-, mid-, and late-stage HCC. • Different perspectives on HCC management between specialties emphasize the importance of multidisciplinary tumor boards. • A multidisciplinary faculty discussed challenging aspects of HCC management, as highlighted by three case studies.

It is difficult to determine whether an individual therapy contributes to the elongation of survival because of the difficulty of organizing clinical research in patients who receive multiple treatments in HCC. We aimed to establish a new model of survival prediction in patients with intermediate stage HCC to establish standards in the recent and coming multi-MTA era. This analysis was prepared using a data set of 753 patients diagnosed HCC prior to 2017. Multiple regression analysis showed age, naïve or recurrence, the size of the largest tumor nodule, the number of nodules, total bilirubin, albumin and α-fetoprotein as independent predictors of survival. A Weibull model had the best fit and, based on these predictors, we established a new predicted survival model. The survival duration can be predicted the proposed model; EXP (4.02580 + (- 0.0086253) × age + (- 0.34667) × (naïve/recurrence) + (- 0.034962) × (number of nodules) + (- 0.079447) × (the size of the largest nodule) + (- 0.21696) × (total bilirubin) + 0.27912 × (albumin) + (- 0.00014741) × (α-fetoprotein)) × (- natural logarithm(0.5))^0.67250. This model is useful for the planning and evaluating the efficacy of recent sequential therapies in multi-MTA era.

Multidrug resistance (MDR) is a major obstacle to the efficacy of hepatocellular carcinoma (HCC) chemotherapy. Previous studies have identified that low FZD3 predicted decreased survival after intraperitoneal versus intravenous-only chemotherapy in ovarian cancer. This study aimed to identify a potential target in HCC chemotherapy. The FZD3 expression variant in HCC cell lines was detected by RT-qPCR and western blotting. The FZD3 expression in the early recurrent HCC group (RE group) and the non-early recurrent HCC group (non-RE group) was measured by RT-qPCR. Then, the 50% inhibitory concentrations (IC50) in HCC cell lines were studied by MTT assay. TOP/FOP FLASH luciferase assay was performed to measure TCF-binding activities. We found that FZD3 was upregulated in three HCC cell lines, and the FZD3 expression was significantly higher in the RE group than in the non-RE group (P = 0.0344). A positive correlation between FZD3 and MDR1 was observed in HCC tissues (R2 = 0.6368, P = 0.0001). Then, we found that FZD3 knockdown significantly altered Huh-7 cell chemotherapeutic sensitivity to cisplatin [50.43 µM in the FZD3 siRNA (siFZD3) group vs 98.59 µM in the siRNA negative control (siNC) group; P = 0.007] or doxorubicin (7.43 µM in the siFZD3 group vs 14.93 µM in the siNC group; P = 0.017). TOP/FOP FLASH luciferase assay showed FZD3 could inhibit Wnt/β-catenin signaling in HCC cells. Moreover, FZD3 expression knockdown in SNU-449 and Huh-7 cells markedly reduced β-catenin and phosho-β-catenin (S37) protein expression, and Cyclin D1, c-myc and MDR1 were significantly decreased. This is the first study to describe the significantly increased FZD3 expression in patients with early recurrent HCC. FZD3 knockdown led to increased sensitivity to chemotherapy by Wnt/β-catenin signaling inhibition in HCC cell lines. Our study suggests FZD3 as a potential target for reversing chemoresistance in HCC.

Postembolization syndrome (PES) represents the most frequent complication after transarterial chemoembolization (TACE) in patients with HCC. Given the vague definition as a symptom complex comprising abdominal pain, fever, and nausea, PES is diagnosed in heterogeneous patient cohorts with symptoms ranging from mild pain to severe deterioration of their general condition. This study aimed to evaluate predictive factors and the prognostic impact of PES with regard to different severity grades.

A total of 954 patients treated with TACE for HCC at the University Medical Centres Mainz and Freiburg were included in this study. PES disease severity was graded as mild, moderate, or severe according to a predefined combination of symptoms. Logistic regression models were used to identify independent predictors of PES. The prognostic impact of PES was evaluated by competing risk analyses considering liver transplantation as a competing risk.

PES occurred in 616 patients (64.5%), but only 56 patients (5.9%) had severe PES, defined as moderate to severe abdominal pain requiring opioids in combination with fever and nausea. The largest tumor diameter was the strongest independent predictor of PES (OR = 1.21, 95% CI = 1.13-1.28), and severe PES (OR = 1.23, 95% CI = 1.14-1.33, p < 0.0001). Presence of liver cirrhosis was protective against PES (OR = 0.48, 95% CI = 0.27-0.84, p = 0.01). Furthermore, PES was independently associated with an impaired disease control rate (OR = 0.33, 95% CI = 0.16-0.69, p = 0.003) and severe PES with poor overall survival (subdistribution HR = 1.53, 95% CI = 0.99-2.36, p = 0.04).

Tumor size and absence of liver cirrhosis are predictors of severe PES and associated with impaired prognosis in HCC patients after TACE.

The last few years have seen a significant increase in the use of technology to manipulate genetic sequences and generate animals as a source of xeno-organs. This has made the generation of genetically bespoke organisms a reality. This paper will analyze the regulatory and practical aspects of such an innovative approach to xenotransplantation on the basis of a hypothetical case study applied to Germany and highlight the gaps in the current regulation. This paper thus provides the basis for legal debate within a specific country. In addition, the identified gaps also pose a barrier toward the harmonization of international regulation. This publication therefore lays the groundwork for guiding the international debate regarding the regulatory framework for solid organ xenotransplantation toward specific issues.

The accurate prediction of postoperative survival time of patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) is important for postoperative health care. Survival analysis is a common method used to predict the occurrence time of events of interest in the medical field. At present, the mainstream survival analysis models, such as the Cox proportional risk model, should make strict assumptions about the potential random process to solve the censored data, thus potentially limiting their application in clinical practice. In this paper, we propose a novel deep multitask survival model (DMSM) to analyze HCC survival data. Specifically, DMSM transforms the traditional survival time prediction problem of patients with HCC into a survival probability prediction problem at multiple time points and applies entropy regularization and ranking loss to optimize a multitask neural network. Compared with the traditional methods of deleting censored data and strong hypothesis, DMSM makes full use of all the information in the censored data but does not need to make any assumption. In addition, we identify the risk factors affecting the prognosis of patients with HCC and visualize the importance of ranking these factors. On the basis of the analysis of a real dataset of patients with BCLC stage B HCC, experimental results on three different validation datasets show that the DMSM achieves competitive performance with concordance index of 0.779, 0.727, and 0.780 and integrated Brier score (IBS) of 0.172, 0.138, and 0.135, respectively. Our DMSM has a comparatively small standard deviation (0.002, 0.002, and 0.003) for IBS of bootstrapping 100 times. The DMSM we proposed can be utilized as an effective survival analysis model and provide an important means for the accurate prediction of postoperative survival time of patients with BCLC stage B HCC.

To compare transarterial chemoembolization delivered with drug eluting beads (TACE-DEB) with stereotactioc body radiation therapy (SBRT) in patients with hepatocellular carcinoma (HCC) in a multicenter randomized trial.

Patients were included if they were eligible for TACE. They could also be recruited if they required treatment prior to liver transplantation. A maximum of four TACE-DEB procedures and ablation after incomplete TACE-DEB were both allowed. SBRT was delivered in six fractions of 8-9Gy. Primary end point was time to progression (TTP). Secondary endpoints were local control (LC), overall survival (OS), response rate (RR), toxicity, and quality of life (QoL). The calculated sample size was 100 patients.

Between May 2015 and April 2020, 30 patients were randomized to the study. Due to slow accrual the trial was closed prematurely. Two patients in the SBRT arm were considered ineligible leaving 16 patients in the TACE-DEB arm and 12 in the SBRT arm. Median follow-up was 28.1 months. Median TTP was 12 months for TACEDEB and 19 months for SBRT (p=0.15). Median LC was 12 months for TACE-DEB and >40 months (not reached) for SBRT (p=0.075). Median OS was 36.8 months for TACEDEB and 44.1 months for SBRT (p=0.36). A post-hoc analysis showed 100% for SBRT 1- and 2-year LC, and 54.4% and 43.6% for TACE-DEB (p=0.019). Both treatments resulted in RR>80%. Three episodes of possibly related toxicity grade ≥3 were observed after TACE-DEB. No episodes were observed after SBRT. QoL remained stable after both treatment arms.

In this trial, TTP after TACE-DEB was not significantly improved by SBRT, while SBRT showed higher local antitumoral activity than TACE-DEB, without detrimental effects on OS, toxicity and QoL. To overcome poor accrual in randomized trials that include SBRT, and to generate evidence for including SBRT in treatment guidelines, international cooperation is needed.

Hepatocellular carcinoma (HCC) is a common malignant tumor, so we need a convenient and objective way to diagnose and treat HCC. We discuss the current situation, progress, hotspots, and existing problems of Albumin-Bilirubin (ALBI) in HCC, which can provide new ideas for the prevention, diagnosis, and treatment of HCC.

We adopt Excel 2019 software and visual analysis tools based on Web of Science database search. This manuscript uses VOSviewer, Co-Occurrence13.3 (COOC13.3) software to conduct overall trend analysis, synonym merging, frequency of countries, journals, institutions, funds, dissimilarity matrices, co-occurrence matrices, bimodal matrices, coupling matrices, cluster analysis of topic evolution time zone graphs.

A total of 610 papers were included, and the number of papers output showed an overall upward trend. ALBI has been valued by the industry in HCC and plays an important role in diagnosing and treating HCC, even better than the classic Child-Pugh (C-P) grade. At the same time, hot spots in the treatment of HCC and other applications of ALBI were discovered.

ALBI score is a convenient and objective liver function evaluation index, which plays an important role in the prediction of patient survival rate and prognosis. Promoting the ALBI score in HCC can help doctors judge the patient's condition and improve the diagnosis and precise treatment effect.

Transarterial chemoembolization (TACE) is the recommended first-line treatment for intermediate-stage Hepatocellular carcinoma (HCC) patients. However, predicting the survival of HCC patients receiving TACE remains challenging.

In this retrospective study, we analyzed a total of 1805 HCC patients who received TACE. The patients were randomly divided into a training set (n = 1264) and a validation set (n = 541). We examined various prognostic factors within the training set and developed a simple ALFP (ALBI grade, AFP, and Prothrombin time) score, which was subsequently validated using the independent validation set.

Our multivariate analysis revealed that baseline ALBI grade 2 or 3, AFP ≥ 100 ng/mL, and PT > 13.1 s were independent unfavorable prognostic factors for HCC patients receiving TACE (p < 0.05). Based on these findings, we constructed the ALFP score, which assigns 1 point each for ALBI grade 2 or 3, AFP ≥ 100 ng/mL, and PT > 13.1 s. The score has a range of 0 to 3, and higher scores are associated with poorer outcomes. The median overall survival (OS) varied significantly among different ALFP score groups, both in the training set and the validation set (p < 0.001). We further examined the ALFP score in subgroups based on tumor diameter and the number of intrahepatic lesions. In each subgroup, higher ALFP scores were consistently associated with lower OS (p < 0.05).

Our study confirms the prognostic value of the ALFP score in predicting the survival of HCC patients undergoing TACE. The score incorporates easily obtainable baseline parameters and provides a simple and practical tool for risk stratification and treatment decision-making in HCC patients.

Hepatocellular carcinoma represents an important cause of death worldwide. Early-stage hepatocellular carcinoma patients not suitable for surgery can be treated with a variety of minimally invasive locoregional interventional oncology techniques. Various guidelines in different countries address the treatment of hepatocellular carcinoma, but the actual treatment is usually discussed by a multidisciplinary tumor board in a personalized manner, leading to potential treatment differences based on Western and Eastern perspectives. The aim of this paper is to integrate literature evidence with the eminent experiences collected during a focused session at the Mediterranean Interventional Oncology (MIO) Live Congress 2023.

Hepatocellular carcinoma (HCC) remains the most common form of liver cancer, accounting for 90% of all primary liver cancers. Up to 30% of HCC cases could be small (2-3 cm in diameter) at the time of diagnosis with advances in imaging techniques and surveillance programmes. Treating patients with early-stage HCC can be complex and often requires interdisciplinary care, owing to the wide and increasing variety of treatment options, which include liver resection, liver transplantation, and various locoregional therapies offered by interventional radiology and radiation oncology. Decisions regarding the optimal management strategy for a patient involve many considerations, including patient- and tumour-specific characteristics, as well as socioeconomic factors. In this review, we aim to comprehensively summarise the commonly used therapies for single, small HCC (<3 cm), with a focus on the impact of tumour size (<2 cm vs. 2-3 cm), as well as a brief discussion on the cost-effectiveness of the different treatment options.

Several breakthroughs in hepatocellular carcinoma (HCC) therapy across tumor stages provide hope to improve its dismal prognosis. Although surgical and local ablative therapies have few significant changes in technique, an improved understanding of tumor biology has facilitated increase numbers of patients who are now eligible to undergo curative-intent procedures. Most notably, acceptable post-transplant outcomes can be achieved in well selected patients whose tumors are downstaged into Milan Criteria. Adjuvant therapy in patients at high risk of recurrence also significantly improves recurrence-free survival after resection or ablation. For patients with liver-localized disease who are not eligible for curative-intent procedures, transarterial chemoembolization (TACE) was historically the treatment modality of choice, regardless of tumor burden; however, there is now increased recognition of patients who are "TACE unsuitable" and may be better treated with systemic therapy. The greatest evolution in HCC treatment options has occurred with systemic therapy, where several new agents are now available in the first- and second-line setting, including immune checkpoint inhibitor combinations. Objective responses are observed in approximately 30% of patients and median survival is approaching 2 years. The availability of immune checkpoint inhibitors has renewed interest in combination therapies for earlier tumor stages, with several phase III trials ongoing. Considering increasing complexities of HCC care, requiring decisions between therapies delivered by different providers, multidisciplinary care is critical and is associated with improved clinical outcomes. In this review, we detail major breakthroughs in HCC therapy, how these breakthroughs can be applied in clinical practice, and remaining areas in need of further research.